The Cancer Biology Program consists of 35 Participating Members, representing total peer-reviewed funding of $16.6 Million in annual direct costs ($23.7 Million in total costs). During the last two years, its Members generated a total of 291 cancer-relevant, peer-reviewed publications, 18% of which were intra- and inter-programmatic collaborations. The Program is focused on molecular mechanisms that convert normal cells into malignant tumors and on characteristics of tumor cells that enable them to escape growth control. It also investigates ways in which they suspend regular differentiation pathways, alter their relationships with neighboring cells and tissues and acquire invasive or metastatic capabilities. Understanding of these mechanisms and properties will facilitate improvement in existing cancer therapies and contribute to the development of new strategies for the diagnosis and treatment of cancer. To achieve its goals, the Cancer Biology Program is composed of the following focus areas: 1. Growth Control: investigation of growth factor and tumor promoter action, cell cycle control and oncogene action. 2. Cellular Interactions in Tumor Development: cell adhesion molecules, glycoproteins and their role in cell-to-cell and cell-matrix interactions, cell invasiveness and metastasis. 3. Responses to Extracellular Stimuli and Stress: mechanisms of signal transduction, cytokine transduction, cytokine biology, cellular responses to genotoxic stress and oncoprotein activation. 4. Basic Cell Biology: protein trafficking within normal and tumor cells, protein turnover and its role in cell regulation. 5. Control of Differentiation and Development: lymphoid and myeloid cell differentiation and transcription regulation. 6. Chemical Biology: Investigation of natural biological compounds and synthetic organic chemicals which exert effects specifically on tumor cells.